The investigator proposes to use the combined approaches of molecular genetics and NMR spectroscopy to probe the structural basis of protein/RNA interactions and to identify new means of preventing them. He proposes a more detailed analysis of the peptide backbone conformation of the RNA binding domain of HIV Tat to map the conformations of the amino-acyl side chains and to determine the structural basis for its strong and unexpected tendency for helix formation. The author then intends to prepare and characterize the complex formed by a short, biologically active Tat peptide with synthetic TAR RNA in order to assess the changes in RNA and protein conformation that occur upon binding and to identify potential targets for inhibitory drug design. The importance of any specific chemical contacts observed will be tested by mutating the nucleotides or amino acids involved and then examining the biologic and structural effects of the mutations.